New vaccinal strategy

Abstract

The present invention relates to the prevention and treatment of disease like cancer. The inventors have previously characterized MELOE-1 antigen as an IRES dependent, melanoma specific translation product from a lncRNA mainly transcribed in the melanocytic lineage. MELOE-1 contains numerous class II epitopes and one HLA-A*0201-restricted CD8 epitope eliciting a frequent repertoire of high avidity T cells. They designed various synthetic long peptide (SLPs) comprising a CD4 epitope coupled to the CD8 epitope by a serie of linkers of 4 to 6 aa and studied the efficacy of T cell clone activation by SLP-loaded DC in vitro. Particularly, they evaluated the ability of a few selected SLPs to stimulate specific T cells proliferation of PBL from healthy donors in vitro and finally, they explored the vaccination potential of their best SLP candidate in vivo in an HLA*A0201 / HLA-DRB0101 transgenic mouse. Thus, the present invention relates a SLP comprising a CD4 class II peptide linked to a CD8 class I peptide by a specific linker and its use in the treatment of disease like cancers.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a specific linker and a synthetic long peptide (SLP) comprising a CD4 class II peptide linked to a CD8 class I peptide by the specific linker. Particularly, the invention relates to the use of the SLP in the treatment of cancers, infectious diseases, inflammatory diseases or auto-immune diseases in a patient in need thereof.BACKGROUND OF THE INVENTION[0002]It is now established that cancer vaccines triggering T cell activation against tumor antigens can be beneficial to cancer patients (1) although many improvements in the vaccination strategies are still necessary to achieve long-term survival of patients. (2). Various immunogens have been tested, ranging from minimal CTL epitope to the full length recombinant protein. Minimal CTL epitope, usually 9-10 amino acids in length led to limited induction of effector T cells associated with disappointing clinical efficacy. This was likely due to the generation of anergic CD8 T c...

AI Technical Summary

Benefits of technology

[0006]The inventors tested linkers to select SLP efficiently processed by antigen presenting cells (APC). After investigations, they concluded that a good sequence for the linker should contain the LSV motif as a core and that a good linker may contain the Xaa1-LSVXaa5-Xaa6 (SEQ ID NO: 1) motif with Xaa1 which can be an amino acid selected in the group consisting in alanine, leucine, valine, serine or Glycine and Xaa5 and Xaa6 which can be an optional amino acids selected in the group consisting in alanine, leucine, valine or Glycine. Such a designed linker allows a cleavage by proteases like cathepsins and thus a good processing of the CD4 class II peptide and the CD8 class I peptide by APC. Moreover, such a linker avoids the formation of neo-antigen which is a really important aspect in the context of a vaccine strategy.

[0055]In one embodiment, the SLP according to the invention comprises at least 70% identity over the SLP of the invention described in the invention, even more particularly at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and is still able to be efficiently processed by antigen presenting cells.

[0100]When provided therapeutically, the vaccine composition of the invention is provided to enhance the patient's own immune response to the melanoma antigen present on the melanoma or metastatic melanoma.

[0121]In a particular embodiment, the T cells are contained in physiological saline, phosphate buffered saline (PBS), culture medium, or the like in order to their stable maintain. Administration may be achieved, for example, intravenously or intra-tumoraly. By returning the T cells that recognizes specifically the antigen peptide of the invention into the patient's body, the toxicity of said T cells, or the stimulation of CD8 cytotoxic T cells by said cells towards tumor cells is enhanced in the patient who is positive for the melanoma antigen peptide of the invention. The tumor cells are destroyed and thereby the treatment of tumor is achieved.

Problems solved by technology

Minimal CTL epitope, usually 9-10 amino acids in length led to limited induction of effector T cells associated with disappointing clinical efficacy.

This anergy probably resulted from exogenous loading of the short epitope and direct presentation to CD8 T cells, thus bypassing intracellular processing of the antigen by DC and co-signaling by matured DC (3) On the other hand, vaccination with full length recombinant proteins does not seem to be the best alternative.

However, no rationale for designing optimal linker is already presented.

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